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Radiological score, asthma and NSAID-exacerbated respiratory disease predict relapsing chronic rhinosinusitis 放射学评分、哮喘和非甾体抗炎药加重的呼吸系统疾病可预测慢性鼻窦炎复发
IF 4.6 2区 医学 Q2 ALLERGY Pub Date : 2025-04-02 DOI: 10.1002/clt2.70043
Markus Lilja, Anni Koskinen, Sari Hammarèn-Malmi, Anu Laulajainen-Hongisto, Jura Numminen, Jyri Myller, Seija Vento, Elina Penttila, Maija Hytönen, Paula Virkkula, Peter W. Hellings, Sven F. Seys, John Lee, Heini Huhtala, Johanna Sahlman, Sanna Toppila-Salmi

Objectives

The aim was to evaluate the predictive potential of Sinonasal Radiological (SR) and the Lund-Mackay (LM) score of sinus computed tomography (CT) scans on postoperative relapses of chronic rhinosinusitis (CRS).

Materials and Methods

CRS patients (n = 483, 12–80 years) underwent routine sinus CT scans. The SR score was defined by obstructed frontal recess (0 = no, 1 = yes) and visualization of middle and inferior turbinate (0 = anatomy can be easily visualized, 1 = anatomy cannot be easily visualized) on each side (a total of 0–6 points). Associations were analyzed by nonparametric, survival and Cox's proportional hazard models.

Results

Revision endoscopic sinus surgery (ESS) was performed in 133 (28.0%) patients on average (min–max) of 3.2 (0–12) years after performing the sinus CT scans. Of the 408 patients who underwent the baseline ESS, high preoperative SR or LM scores significantly predicted revision ESS (p < 0.001) and peroral corticosteroid courses purchased during the follow-up (p = 0.009 and p < 0.001, respectively for SR- and LM-scores). In multivariable analysis, both SR score and asthma and/or NSAID exacerbated respiratory disease (N-ERD) were significantly associated with revision ESS risk (p = 0.035, p = 0.007, respectively).

Conclusion

LM and SR and a history of asthma or N-ERD predict CRS relapses, which may help in decision-making.

目的评价鼻窦CT扫描(CT)鼻窦放射学(SR)和隆德-麦凯(LM)评分对慢性鼻窦炎(CRS)术后复发的预测潜力。材料与方法CRS患者(483例,年龄12 ~ 80岁)行常规鼻窦CT扫描。SR评分以每侧额隐窝阻塞(0 =否,1 =是)和中、下鼻甲可见(0 =解剖易见,1 =解剖不易见)为评分标准(共0 - 6分)。通过非参数、生存和Cox比例风险模型分析相关性。结果133例(28.0%)患者在接受鼻窦CT扫描后平均(最小-最大)为3.2年(0-12)。在408例接受基线ESS的患者中,术前高SR或LM评分显著预测改良ESS (p <;0.001)和随访期间购买的经口皮质类固醇疗程(p = 0.009和p <;SR和lm得分分别为0.001)。在多变量分析中,SR评分、哮喘和/或非甾体抗炎药加重呼吸系统疾病(N-ERD)与改版ESS风险显著相关(p = 0.035, p = 0.007)。结论LM、SR、哮喘史或N-ERD可预测CRS复发,有助于临床决策。
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引用次数: 0
Targeting PDK1: A novel approach to combat hypoxia-induced epithelial-mesenchymal transition in chronic rhinosinusitis with nasal polyps 靶向PDK1:对抗缺氧诱导的慢性鼻窦炎伴鼻息肉的上皮-间质转化的新方法
IF 4.6 2区 医学 Q2 ALLERGY Pub Date : 2025-04-02 DOI: 10.1002/clt2.70048
Sicen Pan, Mengyan Zhuang, Xiangdong Wang, Qinqin Zhang, Ting He, Ying Li, Jian Jiao, Luo Zhang

Background

Hypoxia is a prevalent pathological process in chronic rhinosinusitis with nasal polyps (CRSwNP), leading to a cascade of pathological events, including epithelial-mesenchymal transition (EMT). However, the mechanisms underlying hypoxia-induced EMT remain unclear. This study aims to elucidate the mechanisms driving EMT under hypoxic conditions in CRSwNP.

Methods

Transcriptome and proteome analyses of hypoxia-treated human nasal epithelial cells (HNECs) were performed to identify key molecules and pathways. The expression of hypoxia-inducible factor-1α (HIF-1α), pyruvate dehydrogenase kinase (PDK1), lactate dehydrogenase A (LDHA), and EMT markers was assessed in nasal tissues from CRSwNP patients. In vitro, cultured HNECs were exposed to hypoxia and lactate, or overexpressed PDK1, to evaluate changes in EMT markers.

Results

Hypoxia activated the glycolysis-related pathway in HNECs, with PDK1 and LDHA identified as significantly upregulated glycolysis-related enzymes. The expression of PDK1 and LDHA was closely correlated with HIF-1α and EMT markers in nasal tissues. Hypoxia induced an increase in PDK1 and LDHA expression, lactate production, and EMT occurrence in HNECs. PDK1 overexpression or lactate stimulation also triggered EMT, while PDK1 inhibition attenuated hypoxia-induced EMT in HNECs.

Conclusions

This study is the first to reveal that hypoxia-induced activation of PDK1 plays a critical role in regulating EMT by promoting lactate production, thereby providing a potential therapeutic target for CRSwNP.

缺氧是慢性鼻窦炎伴鼻息肉(CRSwNP)的一个普遍病理过程,导致一系列病理事件,包括上皮-间质转化(EMT)。然而,缺氧诱发EMT的机制尚不清楚。本研究旨在阐明CRSwNP缺氧条件下EMT的驱动机制。方法对缺氧处理的人鼻上皮细胞(HNECs)进行转录组学和蛋白质组学分析,确定关键分子和通路。检测CRSwNP患者鼻组织中缺氧诱导因子-1α (HIF-1α)、丙酮酸脱氢酶激酶(PDK1)、乳酸脱氢酶A (LDHA)和EMT标志物的表达。在体外,培养的hnec暴露于缺氧和乳酸或过表达PDK1中,以评估EMT标志物的变化。结果缺氧激活了nec的糖酵解相关途径,PDK1和LDHA被鉴定为糖酵解相关酶的显著上调。PDK1和LDHA的表达与鼻组织HIF-1α和EMT标志物密切相关。缺氧诱导HNECs中PDK1和LDHA表达增加、乳酸生成和EMT发生。PDK1过表达或乳酸刺激也会引发EMT,而PDK1抑制会减弱缺氧诱导的nec中EMT。本研究首次揭示了缺氧诱导的PDK1激活通过促进乳酸生成在调节EMT中起关键作用,从而为CRSwNP提供了一个潜在的治疗靶点。
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引用次数: 0
Vocal biomarkers correlate with FEV1 variations during methacholine challenge 在甲胆碱刺激期间,声音生物标志物与FEV1变化相关
IF 4.6 2区 医学 Q2 ALLERGY Pub Date : 2025-03-28 DOI: 10.1002/clt2.70055
Giovanni Paoletti, Giovanni Costanzo, Morena Merigo, Francesca Puggioni, Sebastian Ferri, Maria Rita Messina, Fulvio Cordella, Giuseppe Ranieri, Arianna Arienzo, Victor Savevski, Giorgio Walter Canonica, Ayana de Brito Martins, Enrico Heffler

Background

Mobile health applications are increasingly valued for their role in asthma management and the opportunity for large dataset collection. Our study aimed to investigate the feasibility of applying signal-processing and machine-learning technologies to detect alterations in the lower airway caliber and develop a machine-learning algorithm to identify changes in vocal biomarkers and detect bronchoconstriction in patients with airway hyperreactivity.

Methods

This is an explorative observational prospective longitudinal study focused on vocal biomarkers and their association with bronchial constriction and respiratory function. Non-smoker adults with clinical suspicion of asthma were consecutively enrolled from May 2023 to September 2023. At each step of a Methacholine Challenge Test (MCT) performed on these patients, the respiratory sounds were recorded via a smartphone through an app specifically developed. Several biomarkers were extracted and their relationship with the change in Forced Expiratory Volume in the first second (FEV1) was measured.

Results

Forty-two subjects were enrolled. The highest correlation with FEV1 came from exhalation vocal events. No single feature exhibited robust behavior across different subjects, while each subject showed “personal” highly correlated features. All values were strongly statistically significant irrespectively of the result of MCT.

Conclusion

The app’s algorithm is sensitive in correlating specific vocal biomarkers to FEV1 variations during MCT. This feature may assist physicians in diagnosing asthma and its exacerbation and in assessing therapy response and adherence. The socio-economic implications might be significant, and the simplicity of use makes it an ideal tool for research.

移动健康应用程序因其在哮喘管理中的作用和大型数据集收集的机会而越来越受到重视。我们的研究旨在探讨应用信号处理和机器学习技术检测下气道口径变化的可行性,并开发一种机器学习算法来识别声音生物标志物的变化,并检测气道高反应性患者的支气管收缩。方法本研究是一项探索性观察性前瞻性纵向研究,重点研究声乐生物标志物及其与支气管收缩和呼吸功能的关系。从2023年5月至2023年9月,连续入组临床怀疑有哮喘的非吸烟者成人。在对这些患者进行甲基胆碱激发测试(MCT)的每一步中,通过专门开发的应用程序通过智能手机记录呼吸声音。提取了几种生物标志物,并测量了它们与第一秒用力呼气量(FEV1)变化的关系。结果共纳入42例受试者。呼气声事件与FEV1的相关性最高。没有单一的特征在不同的受试者中表现出强大的行为,而每个受试者都表现出“个人”高度相关的特征。与MCT结果无关,所有值均有显著统计学意义。结论该应用程序的算法在MCT期间特异性声乐生物标志物与FEV1变化的相关性方面是敏感的。这一特征可以帮助医生诊断哮喘及其恶化,并评估治疗反应和依从性。社会经济影响可能是重大的,使用简单使其成为理想的研究工具。
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引用次数: 0
Comparing novel treatments in chronic spontaneous urticaria: A critical appraisal of Bruton's tyrosine kinase inhibitors versus anti-cytokine biologics in clinical trials 比较慢性自发性荨麻疹的新治疗方法:布鲁顿酪氨酸激酶抑制剂与抗细胞因子生物制剂在临床试验中的关键评价
IF 4.6 2区 医学 Q2 ALLERGY Pub Date : 2025-03-27 DOI: 10.1002/clt2.70053
Anastasia Diamanti, Chiara Tontini, Silvia Bulfone-Paus
<p>To the Editor,</p><p>We have been following recent clinical trials focusing on new therapies to treat Chronic Spontaneous Urticaria (CSU). While current treatments can manage the debilitating symptoms, a significant number of patients do not achieve symptom control with available medications, including anti-IgE treatment.<span><sup>1, 2</sup></span> New potential solutions to address this include Bruton's tyrosine kinase (BTK) inhibitors, targeting downstream signaling of the Immunoglobulin E high-affinity receptor,<span><sup>3, 4</sup></span> and anti-cytokine biologics, targeting T2/alarmin-driven responses.<span><sup>5</sup></span> However, available literature provides limited comparisons between newer CSU treatments.</p><p>We critically appraised the efficacy and safety of six randomized controlled clinical trials (RCTs), three focusing on BTK inhibitors and three on cytokine blockers, to provide insights into the more promising therapeutic options for CSU. Using the Arksey and O'Malley's framework, we systematically reviewed relevant trials. Our search across Embase and Ovid identified 473 studies from April 2019 to May 2024. A secondary search on ClinicalTrials.gov yielded 123 trials, 15 focusing on BTK inhibitors and cytokine blockers. Based on the CONSORT checklist for methodological quality,<span><sup>6</sup></span> we selected trials scoring a minimum of 10 positive or partially met items out of 25. Six RCTs and two pharmaceutical releases (for trial NCT05107115, whose results were not published at the time of the search) were chosen (Figure 1A, Table 1).</p><p>Common inclusion criteria included CSU duration of at least 6 months and non-response to second-generation H1-antihistamines, while exclusion criteria included recent infections, other dermatological conditions, immunocompromised status, and major health conditions.</p><p>Selected studies were compared across three areas: (A) study characteristics and demographic information (e.g., number of participants, age, gender distribution, ethnic diversity, and dropout rates); (B) CSU outcome measures (e.g., Urticaria Activity Score over 7 days, UAS7); and (C) frequency of serious adverse events.</p><p>Data were normalized for the placebo effect, while statistical differences were as reported by the original authors. Studies NCT03137069 and NCT04180488 involved two cohorts with similar dosage protocols, respectively fenebrutinib 200 mg BID and dupilumab 300 mg SC Q2W. Combined <i>p</i> values were calculated using Fisher's combined probability test, and the survival function of the chi-squared distribution was computed using the <span>chi2.sf</span> function of the <span>scipy</span> Python library.<span><sup>7</sup></span> In studies with multiple dosages, we selected the most effective regimen, resulting in the most significant decrease of UAS7 scores from baseline to endpoint normalized to placebo (Normalized ΔUAS7 = [(UAS7<sub>End of study</sub> – UAS7<sub>Baseline</sub>)]<sub>Tre
致编辑:我们一直在关注最近的临床试验,重点是治疗慢性自发性荨麻疹(CSU)的新疗法。虽然目前的治疗方法可以控制使人衰弱的症状,但相当多的患者无法通过现有的药物控制症状,包括抗ige治疗。新的潜在解决方案包括Bruton的酪氨酸激酶(BTK)抑制剂,靶向免疫球蛋白E高亲和受体的下游信号,3,4和抗细胞因子生物制剂,靶向T2/警报驱动的反应然而,现有文献对较新的CSU治疗方法进行了有限的比较。我们对6项随机对照临床试验(rct)的疗效和安全性进行了严格评估,其中3项针对BTK抑制剂,3项针对细胞因子阻滞剂,以提供对CSU更有希望的治疗选择的见解。使用Arksey和O'Malley的框架,我们系统地回顾了相关的试验。我们在Embase和Ovid上搜索了2019年4月至2024年5月的473项研究。在ClinicalTrials.gov网站上的二次搜索得到123个试验,其中15个集中在BTK抑制剂和细胞因子阻滞剂上。基于CONSORT方法学质量检查表6,我们从25项中选择了至少10项阳性或部分满足的试验。选择了6项随机对照试验和2项药物释放(试验NCT05107115,其结果在检索时未发表)(图1A,表1)。常见的纳入标准包括CSU持续时间至少6个月和对第二代h1 -抗组胺药无反应,而排除标准包括近期感染、其他皮肤病、免疫功能低下状态和主要健康状况。选定的研究在三个方面进行比较:(A)研究特征和人口统计信息(例如,参与者人数、年龄、性别分布、种族多样性和辍学率);(B) CSU结果测量(例如,荨麻疹活动评分超过7天,UAS7);(C)严重不良事件发生频率。根据安慰剂效应对数据进行归一化处理,而统计差异由原作者报告。研究NCT03137069和NCT04180488涉及两个具有相似剂量方案的队列,分别为fenebrutinib 200 mg BID和dupilumab 300 mg SC Q2W。组合p值采用Fisher联合概率检验计算,卡方分布生存函数采用chi2计算。Python库的scipy . sf函数在多剂量的研究中,我们选择了最有效的方案,导致UAS7评分从基线到终点归一化为安慰剂的最显著下降(归一化ΔUAS7 = [(UAS7End of study - UAS7Baseline)]治疗- [(UAS7End of study - UAS7Baseline)]安慰剂)。考虑到随机对照设计和全球临床试验注册,我们认为内部有效性已经建立。相比之下,外部效度是基于代表研究人群的人口统计学/非人口统计学变量来评估的。在选定的6项研究中,有5项研究提供了足够的临床试验方法和结果信息以进行有效性评估(图1B,表1)。尽管可以获得试验结果的初步报告8,9,但当时尚未发表rilzabrutinib/NCT05107115的完整方法学,因此限制了我们的分析。在所有研究中,benralizumab/NCT04612725的平均辍学率最高(32.9%),dupilumab/NCT04180488的平均辍学率最低(0%)。参与者人数134 ~ 311人,平均年龄42.8 ~ 46.4岁,女性占多数(68.7% ~ 77.6%)。种族构成差异很大,非白人参与者的比例从17.7%到37.7%不等。这些研究在安慰剂组和治疗组之间保持了统一的特征,确保了可接受的有效性。然而,潜在的偏倚可能来自不同队列中辍学率、性别和种族组成的细微差异,特别是在fenebrutinib/NCT03137069和dupilumab/NCT04180488试验中。例如,安慰剂组的女性参与者比例(第1组为84.6%,第2组为73.9%)高于非尼布替尼试验中200 mg bid治疗组(第1组为78.6%,第2组为69.6%),安慰剂组(a组为73.5%,B组为75.9%)高于杜匹单抗300 mg Q2W组(a组为58.6%,B组为68.5%)。fenebrutinib 200mg bid治疗组之间的退出率差异显著(队列1 21.4% vs队列2 8.7%)。这些差异可能也导致了各自治疗组中观察到的更显著的UAS7降低。在评估疗效时,四种药物对CSU症状的改善具有统计学意义。给予Remibrutinib 25 mg BID被证明是最有效的,ΔUAS7等于- 12.34 (p &lt;0.0001),而非鲁替尼(200 mg BID)、利扎布替尼(400 mg TID)和杜匹单抗(300 mg Q2W)的范围为- 7。 72至−6.75(图1C)。非尼鲁替尼也显示出最高的控制良好的CSU发生率(30.6%,UAS7≤6)。平均而言,与杜匹单抗相比,基于BTK抑制剂的治疗在ΔUAS7上提供了19%的改善,与所有细胞因子阻滞剂联合相比,提供了55%的改善。然而,抗细胞因子治疗报告的严重不良事件(0%-4%)低于BTK抑制剂(4.65%-5.36%,图1D)。总的来说,瑞米鲁替尼和杜匹单抗是每个药物类别的最佳选择,具有最高的疗效和相对较低的不良事件发生率。总之,我们对BTK抑制剂用于CSU治疗的2期随机对照试验的分析显示,在症状控制方面有更高的疗效,尽管正在进行的3期随机对照试验的结果仍然是有根据的。除dupilumab外,所有分析的研究均未按CSU亚型(即I型与IIb型自身免疫性CSU)或按抗ige治疗反应分层进行治疗反应。因此,目前尚不清楚表现不佳的治疗方法,如抗tslp和IL-5受体抗体,是否可以在特定患者群体和/或相关合共病中提供更好的结果。anastasia Diamanti和Silvia Bulfone-Paus对这项研究进行了概念化。Anastasia Diamanti进行了数据库搜索和统计分析。Anastasia Diamanti和Chiara Tontini创造了人物和桌子。Anastasia Diamanti, Chiara Tontini和Silvia Bulfone-Paus撰写并修改了手稿。作者声明无利益冲突。
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引用次数: 0
Breath of relief: Transforming pediatric asthma care with telemedicine-guided exercises 松一口气:用远程医疗指导的练习改变儿科哮喘护理
IF 4.6 2区 医学 Q2 ALLERGY Pub Date : 2025-03-24 DOI: 10.1002/clt2.70049
Betul Gemici Karaaslan, Hikmet Ucgun, Meltem Kaya, Gokce Nuran Cengiz, Sueda Ozturk, Ozge Barut, Zeynep Korkut, Sezin Aydemir, Zeynep Meric, Birol Topcu, Hilal Denizoglu Kulli, Haluk Cokuğras, Ayca Kiykim

Background

Alternative non-pharmacological strategies such as breathing exercises can be used in combination with pharmacological treatments.

Objective

The aim of this randomized, controlled, single-blind study was to investigate the effectiveness of breathing exercises in asthma patients on respiratory function, symptom control and quality of life.

Methods

We enrolled pediatric asthma patients who were eligible and motivated for the study and randomly assigned them to either the exercise group (EG) or the control group (CG). The CG received a postural exercise program, while the EG received a breathing exercise program. At baseline and after 12 weeks, respiratory function (FEV1-FVC-FEV1/FVC-PEF), symptom control (using asthma control test, asthma control questionnaire, global initiative for asthma symptom control assessment), quality of life (using pediatric asthma quality of life questionnaire), breath-holding test (BHT) and sit-to-stand test (30sSTS) were assessed and compared.

Results

One hundred twelve patients were randomized, and 99 (n = 51 EG, n = 48 CG) completed the 12-week study. Baseline data were also similar in both groups. After 12 weeks, FEV1, Peak expiratory flow (by spirometry and peak flow meter) and BHT were significantly better in EG than in CG (p = 0.01 and p = 0.007 and p = 0.005, respectively). Asthma Control Test and GINA symptom control tool values were also significantly better in both groups.

Discussion

Our participants were children with mild to moderate asthma. We conclude that our results show that breathing exercises can be an effective intervention for children with partially controlled asthma with FEV1,PEF, and BHTs.

背景:替代的非药物治疗策略如呼吸练习可与药物治疗相结合。目的探讨呼吸运动对哮喘患者呼吸功能、症状控制及生活质量的影响。方法我们招募了符合条件且积极参与研究的儿童哮喘患者,并将他们随机分配到运动组(EG)和对照组(CG)。CG组接受姿势训练,EG组接受呼吸训练。在基线和12周后,评估和比较呼吸功能(FEV1-FVC-FEV1/FVC-PEF)、症状控制(采用哮喘控制测试、哮喘控制问卷、全球哮喘症状控制评估倡议)、生活质量(采用儿科哮喘生活质量问卷)、屏气测试(BHT)和坐立测试(30sSTS)。结果随机抽取112例患者,其中99例(51例EG, 48例CG)完成了为期12周的研究。两组的基线数据也相似。12周后,EG组FEV1、呼气峰值流量(肺活量计和峰值流量计)和BHT显著优于CG组(p = 0.01、p = 0.007和p = 0.005)。两组哮喘控制测试和GINA症状控制工具值均显著提高。我们的研究对象是患有轻度至中度哮喘的儿童。我们的结论是,我们的结果表明,呼吸练习可以有效地干预患有FEV1、PEF和bht的部分控制哮喘儿童。
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引用次数: 0
Eosinophils and COVID-19: Insights into immune complexity and vaccine safety 嗜酸性粒细胞与COVID-19:免疫复杂性和疫苗安全性的见解
IF 4.6 2区 医学 Q2 ALLERGY Pub Date : 2025-03-22 DOI: 10.1002/clt2.70050
Wided Sahli, Joana Vitte, Benoit Desnues

Background

COVID-19 exhibits a variety of symptoms and may lead to multi-organ failure and death. This clinical complexity is exacerbated by significant immune dysregulation affecting nearly all cells of the innate and adaptive immune system. Granulocytes, including eosinophils, are affected by SARS-CoV-2.

Objectives

Eosinophil responses remain poorly understood despite early recognition of eosinopenia as a hallmark feature of COVID-19 severity.

Results

The heterogeneous nature of eosinophil responses categorizes them as dual-function cells with contradictory effects. Eosinophil activation can suppress virus-induced inflammation by releasing type 2 cytokines like IL-13 and granular proteins with antiviral action such as eosinophil-derived neurotoxins and eosinophil cationic protein, and also by acting as antigen-presenting cells. In contrast, eosinophil accumulation in the lungs can induce tissue damage triggered by cytokines or hormones like IFN-γ and leptin. Additionally, they can affect adaptive immune functions by interacting with T cells through direct formation of membrane complexes or soluble mediator action. Individuals with allergic disorders who have elevated levels of eosinophils in tissues and blood, such as asthma, do not appear to be at an increased risk of developing severe COVID-19 following SARS-CoV-2 infection. However, the SARS-CoV-2 vaccine appears to be associated with complications and eosinophilic infiltrate-induced immunopathogenicity, which can be mitigated by corticosteroid, anti-histamines and anti-IL-5 therapy and avoided by modifying adjuvants or excipients.

Conclusion

This review highlights the importance of eosinophils in COVID-19 and contributes to a better understanding of their role during natural infection and vaccination.

COVID-19表现出多种症状,并可能导致多器官衰竭和死亡。这种临床复杂性加剧了显著的免疫失调影响几乎所有细胞的先天和适应性免疫系统。包括嗜酸性粒细胞在内的粒细胞受到SARS-CoV-2的影响。尽管早期认识到嗜酸性粒细胞减少是COVID-19严重程度的标志特征,但对嗜酸性粒细胞反应的了解仍然很少。结果嗜酸性粒细胞反应的异质性将其归类为具有相互矛盾作用的双功能细胞。嗜酸性粒细胞激活可以通过释放2型细胞因子如IL-13和具有抗病毒作用的颗粒蛋白,如嗜酸性粒细胞衍生的神经毒素和嗜酸性粒细胞阳离子蛋白,以及作为抗原提呈细胞来抑制病毒诱导的炎症。相反,肺中嗜酸性粒细胞的积累可引起细胞因子或激素如IFN-γ和瘦素引发的组织损伤。此外,它们可以通过直接形成膜复合物或可溶性介质作用与T细胞相互作用,从而影响适应性免疫功能。患有过敏性疾病的个体,如果组织和血液中嗜酸性粒细胞水平升高,如哮喘,在感染SARS-CoV-2后,患严重COVID-19的风险似乎不会增加。然而,SARS-CoV-2疫苗似乎与并发症和嗜酸性粒细胞浸润诱导的免疫致病性有关,这可以通过皮质类固醇、抗组胺药和抗il -5治疗来减轻,并通过修饰佐剂或辅料来避免。结论本综述强调了嗜酸性粒细胞在COVID-19中的重要性,有助于更好地理解其在自然感染和疫苗接种中的作用。
{"title":"Eosinophils and COVID-19: Insights into immune complexity and vaccine safety","authors":"Wided Sahli,&nbsp;Joana Vitte,&nbsp;Benoit Desnues","doi":"10.1002/clt2.70050","DOIUrl":"https://doi.org/10.1002/clt2.70050","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>COVID-19 exhibits a variety of symptoms and may lead to multi-organ failure and death. This clinical complexity is exacerbated by significant immune dysregulation affecting nearly all cells of the innate and adaptive immune system. Granulocytes, including eosinophils, are affected by SARS-CoV-2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Eosinophil responses remain poorly understood despite early recognition of eosinopenia as a hallmark feature of COVID-19 severity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The heterogeneous nature of eosinophil responses categorizes them as dual-function cells with contradictory effects. Eosinophil activation can suppress virus-induced inflammation by releasing type 2 cytokines like IL-13 and granular proteins with antiviral action such as eosinophil-derived neurotoxins and eosinophil cationic protein, and also by acting as antigen-presenting cells. In contrast, eosinophil accumulation in the lungs can induce tissue damage triggered by cytokines or hormones like IFN-γ and leptin. Additionally, they can affect adaptive immune functions by interacting with T cells through direct formation of membrane complexes or soluble mediator action. Individuals with allergic disorders who have elevated levels of eosinophils in tissues and blood, such as asthma, do not appear to be at an increased risk of developing severe COVID-19 following SARS-CoV-2 infection. However, the SARS-CoV-2 vaccine appears to be associated with complications and eosinophilic infiltrate-induced immunopathogenicity, which can be mitigated by corticosteroid, anti-histamines and anti-IL-5 therapy and avoided by modifying adjuvants or excipients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This review highlights the importance of eosinophils in COVID-19 and contributes to a better understanding of their role during natural infection and vaccination.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 3","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Altered diversity and composition of gut microbiota in Korean children with food allergy 韩国食物过敏儿童肠道菌群多样性和组成的改变
IF 4.6 2区 医学 Q2 ALLERGY Pub Date : 2025-03-12 DOI: 10.1002/clt2.70036
Minyoung Jung, Ji Young Lee, Sukyung Kim, Jeongmin Song, Sehun Jang, Sanghee Shin, Min Hee Lee, Mi Jin Kim, Jiwon Kim, Han Byul Lee, Yeonghee Kim, Kangmo Ahn, Minji Kim, Jihyun Kim

Background

This study aimed to comprehensively characterize the gut microbiome and identify individual and grouped gut microbes associated with food allergy (FA) using 16S rRNA gene sequencing.

Methods

Fecal samples were collected from children with IgE-mediated FA and from sex- and age-matched controls. The V3–V4 variable regions of the 16S rRNA gene of the gut microbiome were profiled using next-generation sequencing (Illumina, USA). Bacterial species richness, intracommunity diversity, and intergroup dissimilarity were evaluated. Functional profiles were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) and the Minimal Set of Pathways (MinPath) algorithm.

Results

Fecal samples were collected from children with IgE-mediated FA (n = 66) and from sex- and age-matched controls (n = 22). Gut microbiome richness (p < 0.0001), intra-community diversity (p < 0.0001), and inter-community diversity (p = 0.0004) were higher in the healthy group than in the FA group. Patients with FA were enriched in Blautia, Fusicatenibacter, and Ruminococcus_g5 compared with healthy control individuals (all p < 0.05). Healthy control individuals were significantly enriched in Oscillibacter and Ruminococcus compared with patients with FA (all p < 0.05). Functional pathway analysis identified enrichment in pathways related to endoglucanase in healthy controls and the ATP-binding cassette (ABC) transport system in FA patients.

Conclusions

The gut microbiomes of patients with FA and healthy control individuals had different taxonomic abundances, and the microbiome richness and diversity of the bacterial flora of patients with FA were reduced compared with controls.

本研究旨在通过16S rRNA基因测序,全面表征肠道微生物组,鉴定与食物过敏(FA)相关的个体和肠道微生物群。方法收集ige介导的FA患儿和性别、年龄相匹配的对照组的粪便样本。使用下一代测序(Illumina, USA)对肠道微生物组16S rRNA基因的V3-V4可变区进行了分析。对细菌种类丰富度、群落内多样性和群间差异性进行了评价。利用重构未观察状态(PICRUSt)和最小路径集(MinPath)算法对群落的系统发育调查进行了功能预测。结果收集了ige介导的FA患儿(n = 66)和性别和年龄匹配的对照组(n = 22)的粪便样本。肠道菌群丰富度(p <;0.0001),群落内多样性(p <;0.0001),健康组的群落间多样性(p = 0.0004)高于FA组。与健康对照组相比,FA患者中Blautia、Fusicatenibacter和Ruminococcus_g5含量丰富(p <;0.05)。与FA患者相比,健康对照个体的Oscillibacter和Ruminococcus显著富集(p <;0.05)。功能通路分析发现,健康对照中与内切葡聚糖酶相关的通路富集,FA患者中与atp结合盒(ABC)运输系统相关的通路富集。结论FA患者与健康对照者肠道菌群的分类丰度存在差异,FA患者肠道菌群的丰富度和多样性均低于对照组。
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引用次数: 0
Epicutaneous immunotherapy for food allergy: A systematic review and meta-analysis 表皮免疫疗法治疗食物过敏:系统回顾和荟萃分析
IF 4.6 2区 医学 Q2 ALLERGY Pub Date : 2025-03-02 DOI: 10.1002/clt2.70045
Péter Csonka, Bohee Lee, Ilari Kuitunen

Background

Food allergies pose a global healthcare challenge, underscoring the need for effective interventions. This study evaluated the efficacy and safety of epicutaneous immunotherapy (EPIT) for food allergen desensitisation.

Methods

We conducted a systematic review of randomised controlled trials by searching Ovid EMBASE, PubMed and Scopus in April 2024. Using a random-effects meta-analysis, we evaluated the clinical effectiveness and harms of EPIT, reporting results as risk ratios with 95% confidence intervals (CI).

Results

After screening 460 abstracts and 35 full reports, 11 were included: nine on peanuts and two on cow's milk (CM). Peanut EPIT had a 51.2% treatment response versus 22.4% for placebo (RR 2.16, CI 1.49–3.12; four studies; moderate certainty). The RR for milk EPIT response rate was 1.78 (CI 1.06–3.00; one study). Five peanut studies (1396 patients) reported EPIT-related adverse events (RR 1.39, CI 0.94–2.05; low certainty).

Conclusions

EPIT offers a moderate treatment response with a favourable safety profile and significant improvements in quality of life. Current knowledge of EPIT remains limited, with evidence confined to peanut and CM allergies. There is a lack of research on sustained unresponsiveness achieved through food EPIT.

食物过敏是一个全球性的卫生保健挑战,强调需要有效的干预措施。本研究评估了表皮免疫疗法(EPIT)对食物过敏原脱敏的有效性和安全性。方法通过检索Ovid EMBASE、PubMed和Scopus,于2024年4月对随机对照试验进行系统评价。采用随机效应荟萃分析,我们评估了EPIT的临床疗效和危害,并以95%置信区间(CI)的风险比报告结果。结果筛选460篇摘要和35篇完整报道,最终纳入11篇:9篇花生,2篇牛奶。花生EPIT治疗有效率为51.2%,安慰剂为22.4% (RR 2.16, CI 1.49-3.12;四个研究;温和的确定性)。牛奶EPIT反应率的RR为1.78 (CI 1.06-3.00;一项研究)。5项花生研究(1396例患者)报告了epit相关不良事件(RR 1.39, CI 0.94-2.05;低确定性)。结论:EPIT提供了一个中等的治疗反应,具有良好的安全性和显著的生活质量改善。目前对EPIT的了解仍然有限,证据仅限于花生和CM过敏。缺乏通过食品EPIT实现的持续无反应性的研究。
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引用次数: 0
Sex disparity in adult asthma—A potential immunomodulatory role of let-7 family microRNAs 成人哮喘的性别差异——let-7家族microrna的潜在免疫调节作用
IF 4.6 2区 医学 Q2 ALLERGY Pub Date : 2025-02-28 DOI: 10.1002/clt2.70042
Carina Malmhäll, Jenny Calvén, Julie Weidner, Kristina Johansson, Patricia Ramos-Ramírez, Emma Boberg, Linda Ekerljung, Roxana Mincheva, Bright Nwaru, Hannu Kankaanranta, Henric Olsson, Christopher McCrae, Madeleine Rådinger

Background

Sex differences have been reported in the incidence, prevalence and severity of asthma. Previous findings from animal models have revealed sex-related differences in inflammatory pathways that may contribute to asthma pathogenesis, but human studies are limited.

Methods

Airway and blood samples (n = 55 and n = 85 respectively) were collected from adult females and males with asthma and healthy subjects. Type 2 innate lymphoid cells (ILC2s), T helper (Th)2 cells and their expression of IL-33R/ST2 (ST2L) were evaluated by flow cytometry. IL-13, thymic stromal lymphopoietin (TSLP), IL-33 and soluble IL-33R/ST2 (sST2) were measured by ELISA. Let-7 miRNA expression in bronchial biopsies was determined by qPCR.

Results

Females with asthma reported more exacerbations and had a higher number of airway eosinophils compared with males with asthma. Bronchial biopsy expression of Let-7f, Let-7g and miR-98 tended to be higher in males with asthma compared with females and inversely correlated with asthma exacerbations. In contrast, increased levels of IL-13, TSLP and sST2 were found in females with asthma compared with males.

Conclusion

Our study demonstrates different inflammatory signatures between males and females with asthma. Let-7 miRNAs act as immune modulators by inhibiting the production of IL-13 and may be an important factor explaining the sex disparity seen in asthma.

研究背景:在哮喘的发病率、患病率和严重程度上存在性别差异。先前动物模型的研究结果表明,炎症途径的性别差异可能导致哮喘发病,但人类研究有限。方法对成年哮喘患者(男、女)和健康人(男、女)分别采集气道和血液标本55份和85份。流式细胞术检测2型先天淋巴样细胞(ILC2s)、辅助性T细胞(Th)2及其IL-33R/ST2 (ST2L)的表达。ELISA法检测IL-13、胸腺基质淋巴生成素(TSLP)、IL-33和可溶性IL-33R/ST2 (sST2)。采用qPCR检测支气管活检组织中Let-7 miRNA的表达。结果与男性哮喘患者相比,女性哮喘患者有更多的急性发作和气道嗜酸性粒细胞数量。支气管活检中Let-7f、Let-7g和miR-98的表达在男性哮喘患者中高于女性,且与哮喘加重呈负相关。与男性相比,女性哮喘患者IL-13、TSLP和sST2水平升高。结论我们的研究表明,男性和女性哮喘患者的炎症特征不同。Let-7 mirna通过抑制IL-13的产生作为免疫调节剂,可能是解释哮喘性别差异的一个重要因素。
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引用次数: 0
CCL2/C–C chemokine receptor type 2-mediated interactions among mast cells, basophils, and endothelial cells 肥大细胞、嗜碱性细胞和内皮细胞之间CCL2/ C-C趋化因子受体2型介导的相互作用
IF 4.6 2区 医学 Q2 ALLERGY Pub Date : 2025-02-23 DOI: 10.1002/clt2.70044
Maruša Rihar, Rajia Bahri, Vida Forstnerič, Silvia Bulfone-Paus, Peter Korošec

Background

IL-33 is involved in allergic processes by promoting the release of various mast cell (MC) chemokines, including CCL2. However, it is yet unclear which specific cell type is primarily responsible for producing CCL2 during acute allergic reactions. This study aims to investigate the role of IL-33 in promoting CCL2 production in mast cells and assess the effect of MC-derived CCL2 on basophil migration and endothelial permeability.

Methods

Human blood-derived MCs (hMCs) were generated from peripheral blood precursors, passively sensitized with IgE, treated with IL-33, and stimulated with anti-IgE. The concentrations of nine cytokines known to influence immune cell chemotaxis (CCL2, CCL5, CCL11, MIP-1α, IL-8, IL-10, IL-13, granulocyte-macrophage colony-stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF) were assessed in the supernatants of hMCs. Subsequently, we investigated the impact of MC-derived CCL2 on basophil migration in vitro, as well as its effect on endothelial monolayer permeability using human umbilical vein endothelial cells (HUVECs).

Results

Stimulation with anti-IgE induced a significant release of CCL2, GM-CSF, IL-8 and VEGF from hMCs. Additionally, incubation with IL-33 overnight increased the production of several cytokines. Mast cell-derived CCL2 not only enhanced basophil migration in vitro but also increased endothelial monolayer permeability in HUVECs. The effect was reversed by a C–C chemokine receptor type 2 (CCR2) antagonist, indicating the involvement of CCL2 signaling through the CCR2 receptor.

Conclusions

IL-33 induces the production of chemotactic cytokines in hMCs. Mast cell-derived CCL2 plays an important role in basophil chemotaxis in vitro and affects endothelial monolayer permeability in the HUVEC model.

IL-33通过促进包括CCL2在内的各种肥大细胞(MC)趋化因子的释放参与过敏过程。然而,目前尚不清楚哪种特定的细胞类型在急性过敏反应中主要负责产生CCL2。本研究旨在探讨IL-33在肥大细胞中促进CCL2生成的作用,并评估mc源性CCL2对嗜碱性粒细胞迁移和内皮细胞通透性的影响。方法利用人外周血前体制备人血源性MCs (hMCs),经IgE被动致敏,IL-33处理,抗IgE刺激。在hmc的上清液中评估了已知影响免疫细胞趋化性的九种细胞因子(CCL2、CCL5、CCL11、MIP-1α、IL-8、IL-10、IL-13、粒细胞-巨噬细胞集落刺激因子(GM-CSF)和血管内皮生长因子(VEGF)的浓度。随后,我们利用人脐静脉内皮细胞(HUVECs)研究了mc来源的CCL2对体外嗜碱性粒细胞迁移的影响,以及对内皮单层通透性的影响。结果抗ige刺激可诱导hmc细胞释放CCL2、GM-CSF、IL-8和VEGF。此外,与IL-33孵育过夜增加了几种细胞因子的产生。肥大细胞源性CCL2不仅增强了体外嗜碱性粒细胞迁移,而且增加了HUVECs内皮单层通透性。这种作用被C-C趋化因子受体2型(CCR2)拮抗剂逆转,表明CCL2信号通过CCR2受体参与。结论IL-33可诱导hmc细胞产生趋化因子。肥大细胞来源的CCL2在体外嗜碱性粒细胞趋化中发挥重要作用,并影响HUVEC模型内皮单层通透性。
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期刊
Clinical and Translational Allergy
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